Early Alzheimer's Disease Group Research Articles

Comparative Analysis of Retinal Structural and Angiographic Parameters in Diabetic Patients, Alzheimer's Disease Patients, and Healthy Controls: An OCT-Based Study.

Objective: This study aimed to investigate the potential connections between Alzheimer's Disease (AD) and diabetes. Methods: This is a cross-sectional study in which AD and diabetes patients sent by the Psychiatry and Diabetes Departments for ophthalmological screening were observed for inclusion/exclusion criteria. Patients were divided into two comparison groups. The first group (n=3) consisted of the age-matched normal and diabetic patient of the stage 3 AD disease participant. The second group (n=3) was for the stage 5 AD patient with diabetes and normal age-matched controls. Each patient underwent a full ophthalmological examination and SS-OCT (Swept Source-Ocular Computer Tomography) for retinal evaluation. Results: A total of 6 patients (12 eyes) were obtained, three men and three women. In the early AD group, the patient with diabetes showed lower macular thickness compared to other groups. In the nasal-inferior (NI) and temporal-superior (TS) ganglion cell layer (GCL), the AD patient showed statistically significant lower values compared to the other patients. In the moderately severe AD group, we found that the AD patient had lower retinal nerve fiber layer (RNFL) thickness on the temporal side compared to the rest of the patients and both the AD patient and diabetes patient showed lower RNFL thickness in the nasal-superior (NS) quadrant. Also, the foveal avascular zone (FAZ) area was statistically significantly lower for both the diabetes and AD patients compared to the healthy control. Conclusions: In conclusion, distinct retinal findings associated with AD and diabetes in young and elderly patients were revealed in our study. The clinical implications and potential interplay between these conditions need to be elucidated by further research. Abbreviations: AD = Alzheimer's Disease, SS-OCT = Swept Source - Ocular Computer Tomography, GCL = Ganglion cell layer, RNFL = Retinal nerve fiber layer, FAZ = foveal avascular zone.

Reduced Limbic and Hypothalamic Volumes Correlate with Bone Density in Early Alzheimer's Disease

Accelerated bone loss is associated with Alzheimer's disease (AD). Although the central nervous system plays a direct role in regulating bone mass, primarily through the actions of the hypothalamus, there is little work investigating the possible role of neurodegeneration in bone loss. In this cross-sectional study, we examined the association between bone mineral density (BMD) and neuroimaging markers of neurodegeneration (i.e., global and regional measures of brain volume) in early AD and non-demented aging. Fifty-five non-demented and 63 early AD participants underwent standard neurological and neuropsychological assessment, structural MRI scanning, and dual energy x-ray absorptiometry. In early AD, voxel-based morphometry analyses demonstrated that low BMD was associated with low volume in limbic grey matter (GM) including the hypothalamus, cingulate, and parahippocampal gyri and in the left superior temporal gyrus and left inferior parietal cortex. No relationship between BMD and regional GM volume was found in non-demented controls. The hypothesis-driven region of interest analysis further isolating the hypothalamus demonstrated a positive relationship between BMD and hypothalamic volume after controlling for age and gender in the early AD group but not in non-demented controls. These results demonstrate that lower BMD is associated with lower hypothalamic volume in early AD, suggesting that central mechanisms of bone remodeling may be disrupted by neurodegeneration.

Early Deficits in Cortical Control of Swallowing in Alzheimer's Disease

The goal of this study was to determine whether functional changes in cortical control of swallowing are evident in early Alzheimer's disease (AD), before dysphagia (swallowing impairment) is evident. Cortical function was compared between an early AD group and a group of age-matched controls during swallowing. Swallowing oropharyngeal biomechanics examined from videofluoroscopic recordings were also obtained to more comprehensively characterize changes in swallowing associated with early AD. Our neuroimaging results show that the AD group had significantly lower Blood-Oxygen-Level-Dependent (BOLD) response in many cortical areas that are traditionally involved in normal swallowing (i.e., pre and postcentral gyri, Rolandic and frontal opercula). There were no regions where the AD group showed more brain activity than the healthy controls during swallowing, and only 13% of all active voxels were unique to the AD group, even at this early stage. This suggests that the AD group is not recruiting new regions, nor are they compensating within regions that are active during swallowing. In videofluoroscopic measures, the AD group had significantly reduced hyo-laryngeal elevation than the controls. Although, swallowing impairment is usually noted in the late stages of AD, changes in cortical control of swallowing may begin long before dysphagia becomes apparent.

Bone Density and Brain Atrophy in Early Alzheimer's Disease

Studies suggest a link between bone loss and Alzheimer's disease. To examine bone mineral density (BMD) in early Alzheimer's disease (AD) and its relationship to brain structure and cognition, we evaluated 71 patients with early stage AD (Clinical Dementia Rating (CDR) 0.5 and 1) and 69 non-demented elderly control participants (CDR 0). Measures included whole body BMD by dual energy x-ray absorptiometry (DXA) and normalized whole brain volumes computed from structural MRI scans. Cognition was assessed with a standard neuropsychological test battery. Mean BMD was lower in the early AD group (1.11 +/- 0.13) compared to the non-demented control group (1.16 +/- 0.12, p = 0.02), independent of age, gender, habitual physical activity, smoking, depression, estrogen replacement, and apolipoprotein E4 carrier status. In the early AD group, BMD was related to whole brain volume (b = 0.18, p = 0.03). BMD was also associated with cognitive performance, primarily in tests of memory (logical memory [b = 0.15, p = 0.04], delayed logical memory [b = 0.16, p = 0.02], and the selective reminding task - free recall [b = 0.18, p = 0.009]). BMD is reduced in the earliest clinical stages of AD and associated with brain atrophy and memory decline, suggesting that central mechanisms may contribute to bone loss in early AD.

Heterogeneity of posterior limbic perfusion in very early Alzheimer's disease

Purpose This study was designed to quantify the heterogeneity of cerebral perfusion on SPECT images in elderly controls and Alzheimer's disease (AD) patients in mild stage using a three-dimensional fractal analysis (3D-FA). Material and method Seventy-five patients with possible and probable AD based on the NINCDS/ADRDA criteria, and thirty-one elderly controls underwent 99mTc-HMPAO SPECT scanning. Dementia severity was assessed using the clinical dementia rating (CDR). Patients with CDR scores of 0.5 ( n = 33) were classified as “very early” and those with CDR 1 ( n = 42) as “early”. We delineated the SPECT images using 2 cutoffs (35% and 50% cutoffs of the maximal voxel radioactivity) and measured the number of voxels in the areas included by the contours obtained with each cutoff level. The fractal dimension (FD) was calculated by relating the logarithms of cutoff level and the number of voxels. Posterior limbic images were reconstructed at 30° positive to the coronal plane, and posterior limbic FD was calculated. Result Posterior limbic FD for early AD, very early AD, and control groups were 1.03 ± 0.16, 1.02 ± 0.17, and 0.87 ± 0.14 ( P = 0.001 versus early AD group, P = 0.001 versus very early AD). Use of the posterior limbic FD and the ratio of posterior limbic FD to total FD separated very early AD patients from controls with a sensitivity of 76% and a specificity of 81%. Conclusion 3D-FA indicated significant differences in the heterogeneity of CBF distribution between patients with AD in mild stage and elderly controls. Posterior limbic FD may be useful for easily and objectively distinguishing patients with very early AD from aging people.

Comparison of temporal order memory in early and middle stage Alzheimer's disease

Four tests, each including a new learning and a prior learning component were developed to investigate temporal order memory in subjects with early and middle stage Alzheimer's disease (AD). For newly learned information, both AD groups performed worse than controls but did not differ from each other. For previously learned information, the subjects with AD performed worse than controls. The early AD group performed better than the middle AD group. It appears then, that progression of the disease is associated with decreased access to knowledge systems.